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1996-01-30
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Document 0414
DOCN M9610414
TI Regulation by corticosteroids of Th1 and Th2 cytokine production in
human CD4+ effector T cells generated from CD45RO- and CD45RO+ subsets.
DT 9601
AU Brinkmann V; Kristofic C; Department of Asthma/Allergy Research,
Ciba-Geigy Ltd., Basel,; Switzerland.
SO J Immunol. 1995 Oct 1;155(7):3322-8. Unique Identifier : AIDSLINE
MED/96015975
AB Corticosteroids (CS) are widely used as immunosuppressive and
anti-inflammatory agents, but their mechanism of action is not well
understood. In this study we analyzed the effects of CS on the growth
and differentiation of human CD4+45RO- naive and CD4+45RO+ memory T
cells. To generate effector T cells secreting large amounts of Th1 and
Th2 cytokines, FACS-sorted naive and memory subsets were primed and
restimulated in vitro via the TCR in the presence of IL-2. CS added
during priming reduced clonal expansion of both T cell populations, but
the memory subset was 100-fold less sensitive. At lower concentrations,
CS favored the development of effector T cells (from both subsets),
which upon restimulation produced large amounts of the anti-inflammatory
cytokine IL-10, but low amounts of IL-4, IL-5, or IFN-gamma.
Interestingly, CS displayed different effects if it was added only
during the restimulation of effector T cells. CS were unable to suppress
clonal expansion of restimulated effector T cells. In effector T cells
derived from the naive subset, CS induced production of IL-4 and IL-10,
but blocked production of IL-5 and IFN-gamma. In effector T cells
generated from the memory subset, CS blocked production of IL-4, IL-5,
and IL-10, but inhibited production of IFN-gamma by only 50%, even if
100-fold higher concentrations of CS were applied. These results
indicate that persistent TCR stimulation, e.g., in chronic infection,
may reduce the sensitivity of T cells to the antiproliferative effects
of CS. Furthermore, the potential of CS to increase or suppress IL-4 and
IL-10 production depending on the stage of T cell activation may explain
in part the beneficial effects of CS in the treatment of acute
inflammation and chronic allergic/asthmatic diseases.
DE Adrenal Cortex Hormones/*PHARMACOLOGY Antigens, CD4/*IMMUNOLOGY
Antigens, CD45/*IMMUNOLOGY Cell Differentiation/DRUG EFFECTS Cells,
Cultured Cytokines/*BIOSYNTHESIS CD4-Positive T-Lymphocytes/DRUG
EFFECTS/*IMMUNOLOGY Human Th1 Cells/IMMUNOLOGY Th2 Cells/IMMUNOLOGY
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).